Pulmonary fibrosis in patients with COVID-19 tends to resolve, while idiopathic pulmonary fibrosis always progresses Scientists believe key immune elements – cells and genes – may explain resolution versus progression of the disease “Both diseases are caused by injury to alveolar epithelial cells in the lungs. In the case of COVID-19, the injury is viral and acute and in the case of IPF, the injury is unknown but repetitive and chronic — so that may explain the different patterns of pulmonary fibrosis progression.’’ TAMPA, Fla. (Jan. 23, 2025) – Pulmonary fibrosis is a rare, chronic disease that causes scarring in the lungs, making breathing difficult for people who suffer with it.
And, as University of South Florida pulmonologist Dr. Jose Herazo-Maya knows all too well, it is generally irreversible.
But when Herazo-Maya, director of the Ubben Center for Pulmonary Fibrosis Research and an associate professor at the USF Health Morsani College of Medicine, began studying patients who developed pulmonary fibrosis after contracting severe cases of COVID-19, he and his research team noticed something strange.
The patients’ lungs got better.
“The importance of this finding is that pulmonary fibrosis after COVID-19 tends to resolve, while in idiopathic pulmonary fibrosis (IPF) it always progresses,” Herazo-Maya said. “We need to learn about the factors associated with pulmonary fibrosis resolution and apply it to non-resolving forms of pulmonary fibrosis.”
The team’s findings are published in print this month in the American Journal of Physiology in a paper entitled Convergent and Divergent Immune Aberrations in COVID-19, post-COVID-19-Interstitial Lung Disease and Idiopathic Pulmonary Fibrosis. Herazo-Maya is the senior author.
One key question is whether researchers can apply what they’ve learned from these COVID-19 patients to patients who have IPF, the most common form of pulmonary fibrosis.
Herazo-Maya believes they can, and he is studying the effects of severe COVID on people who subsequently developed pulmonary fibrosis and applying that knowledge to develop new treatments to improve survival in patients with both conditions.
Since COVID-19 started, Herazo-Maya and his team have been investigating the similarities between abnormal levels of genes in the blood of patients with IPF and COVID. These new findings build on scientists’ previous understanding by addressing the identification of the immune cells where the genes are activated or deactivated and their relationship in the two diseases.
“In the present manuscript, which is a follow up of our initial work, we wanted to study the cellular origin of these genes in COVID-19 and IPF,’’ Herazo-Maya said. “This time, we also studied patients with post-COVID-19-interstitial lung disease -- that is, pulmonary fibrosis that happens as a result of COVID-19. To achieve this goal, we used single-cell RNA sequencing, a novel technique that allows us to study the entire human genome in each single cell from patients.’’
The new findings describe how certain genes in monocytes – white blood cells in the immune system – orchestrate suppression of T cells in the blood, leading to increased risk of death in COVID-19. The study involved a suppressor cell called 7-Gene-M-MDSC – short for monocytic myeloid derived suppressive cells.
“What this means is that 7-Gene-M-MDSC are associated with increased risk of COVID-19 mortality, but if you survive severe COVID-19 and end up having pulmonary fibrosis as a result, the pulmonary fibrosis is self-limited and not progressive,’’ said lead author, Bochra Tourki, a member of Herazo-Maya’s team. “We think this is because of the disappearance of the 7-Gene-M-MDSC and the resurgence of T cell responses.’’
T cells are a type of white blood cell that help the immune system fight germs and ward off disease. But why does pulmonary fibrosis in post-COVID-19 tend to resolve while it progresses in people with IPF who aren’t sick from COVID-19?
“Both diseases are caused by injury to alveolar epithelial cells in the lungs,’’ Herazo-Maya explained. “In the case of COVID-19, the injury is viral and acute and in the case of IPF, the injury is unknown but repetitive and chronic — so that may explain the different patterns of pulmonary fibrosis progression. What we found in this study were the key immune elements (cells and genes) that may explain resolution versus progression of pulmonary fibrosis.’’
IPF affects the tissue surrounding the air sacs, or alveoli, in the lungs. This condition develops when lung tissue becomes thick and stiff for reasons still unknown and leads to the irreversible lung scarring that makes breathing difficult.
The new research is a follow up of Herazo-Maya’s previous work in pinpointing genes to predict lung fibrosis outcomes. The primary goal of his ongoing research is to identify genes that predict outcomes for people with lung fibrosis, because by targeting these genes, researchers might be able to develop new treatments to help improve survival rates.
“We believe that the opportunity is to modulate the expression of genes identified in this study as a way to treat acute COVID-19, post-COVID-19 pulmonary fibrosis and IPF,’’ he said.
This raises the possibility that blocking the expression of genes in monocytes or increasing the expression of certain genes in T cells may turn a disease that always progresses into a form of pulmonary fibrosis that can be treated.
“In the future,’’ Herazo-Maya said, “strategies aiming at modulating the cells that cause these genes to change may lead to novel therapies that could improve COVID-19 survival.’’
Notes:
The study was performed with research funding from the National Institutes of Health and the USF Ubben Center for Pulmonary Fibrosis Research. The manuscript was selected as one of the best research articles in January 2025 by the American Physiological Society because of the relevance of its findings Researchers from the following institutions also contributed: Tampa General Hospital, the University of Pittsburgh, Carnegie Mellon-University, the University of Patras, Greece and the University of Florida.
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